Optimised and Rapid Pre-clinical Screening in the SOD1G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis (ALS)

The human SOD1G93A transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust preclinical data in these models has been highlighted as an area for concern. Secondly, the amount of time required for a single preclinical experiment in these models (3–4 months) is a hurdle to the development of new therapies. We have developed an inbred C57BL/6 mouse line from the original mixed background (SJLxC57BL/6) SOD1G93A transgenic line and show here that the disease course is remarkably consistent and much less prone to background noise, enabling reduced numbers of mice for testing of therapeutics. Secondly we have identified very early readouts showing a large decline in motor function compared to normal mice. This loss of motor function has allowed us to develop an early, sensitive and rapid screening protocol for the initial phases of denervation of muscle fibers, observed in this model. We describe multiple, quantitative readouts of motor function that can be used to interrogate this early mechanism. Such an approach will increase throughput for reduced costs, whilst reducing the severity of the experimental procedures involved

Implication des facteurs périnataux dans le développement des Troubles du Spectre Autistique : cas particulier des naissances par césarienne programmée

Worldwide, an estimate of 0.62% of children is diagnosed with Autism Spectrum Disorder (ASD) and the prevalence has increased considerably in the last decades. Genetics and environment including prenatal and perinatal factors have been suspected to interact in the causation of ASI). Recent report indicates that oxytocin-mediated neuroprotective yaminobutyric acid (GABA) exctitatory-inhibition shift during delivery is abolished in rodent models of autism. Programmed Caesarean Section (CS) is an obstetrical situation in which there is no oxytocin produced. Blocking oxytocin signaling in rat or mice mothers mimics this situation and produced offspring having electrophysiological and behavioral autistic-like features. Therefore the present work aimed at screening the literature for the perinatal factors associated to development of autism spectrum disorders with the special scope of programmed caesarean section. Delivery by CS is associated with a modest increased odd of ASD Specific impact of programmed CS is however poorly studied. Pooled Odd Ratio (OR) from few studies that reported adjusted estimates for elective CS was not significant. Given the growing prevalence of birth by programmed CS worldwide this warrants further investigation.On estime qu'un diagnostic de Trouble du Spectre Autistique (TSA) est posé chez 0.62% d'enfants dans le monde et la prévalence de TSA a augmenté considérablement au cours des derniers décades. Des facteurs génétiques et environnementaux y compris des facteurs pré et périnataux ont été suspectés d'interagir dans le développement des TSA. Récemment une étude rapporte que la transition de l'effet excitateur de l'acide y-aminobutyrique (GABA) vers un effet inhibiteur induite par l'ocytocine au moment de la naissance est abolie dans des modèles murins d'autisme. Les césariennes programmées sont des situations obstétricales au cours desquelles il n'y a pas d'ocytocine produite. Le blocage de la signalisation induite par l'ocytocine mime ces situations et entraine la naissance de nouveaux nés ayant une signature électrophysiologique neuronale et des comportements autistes. Ce mémoire a donc eu pour but de parcourir la littérature traitant des facteurs périnataux associés au développement de TSA en s'intéressant aux naissances césariennes programmées. Les naissances par césariennes sont associées à une augmentation modeste du rapport de chance (Odd Ratio) de TSA. L'influence des césariennes programmées est en revanche peu étudiée. L'augmentation du rapport de chance cumulé des études existantes n'est pas significative. Au vu de l'augmentation du nombre de césariennes programmées dans le monde d'autres études sont nécessaires

Knowledge and attitudes of midwives regarding reprotoxic agents during pregnancy: snapshot of the Marseille area, southern France.

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Analysis of reprotoxic environmental exposures in infertile patients

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Environmental Health in Perinatal and Early Childhood: Awareness, Representation, Knowledge and Practice of Southern France Perinatal Health Professionals

International audienceThe exposure of adults of reproductive age as well as pregnant women and children to environmental contaminants is of particular concern, as it can impact fertility, in utero development, pregnancy outcomes and child health. Consequently, the World Health Organisation (WHO) and international societies advocate including Environmental Health (EH) in perinatal care, yet perinatal health professionals (HPs) hardly put these recommendations into practice. In 2017, a cross-sectional study was performed in a large panel of perinatal HPs in south-eastern France with the aim of painting a picture of their current attitudes, representation, knowledge, and training expectations. Quantitative and qualitative information was collected via auto-questionnaire. Questionnaires were completed by 962 participants, mainly midwives (41.1%), physicians (25.6%) and nursery nurses (11%). Indoor/outdoor air quality and endocrine disruptors were the best-mastered topics, whereas electromagnetic fields and diet gave rise to unsure responses. Overall, perinatal HPs were ill-trained and -informed about the reproductive risks linked to daily environmental exposure. HPs reported scarce knowledge, fear of patient reaction and lack of solutions as the main barriers to providing information regarding EH to the public. Our findings highlight the need to set up EH training programmes focused on scientific knowledge and to provide simple messages and tips to help perinatal HPs deliver advice to populations to mitigate exposure to environmental toxicants

Nomograms for predicting adverse obstetric outcome in IVF pregnancy: A preliminary study

International audienceBackground: In a previous study, we showed that the obstetric complication rate after in vitro fertilization (IVF) pregnancy was 40%. The main objective of our study was to determine maternal prognosis factors that influence the IVF pregnancy outcome.Methods: We conducted an observational retrospective monocentric study between January 2014 and January 2018. Pregnancy over 22 gestational weeks (GW) obtained after IVF in our infertility clinic was included. Maternal characteristics and pregnancy outcome were collected.Results: Data from 498 IVF pregnancies were analyzed. The most significant maternal prognosis factors for obstetric complications were maternal age above 40 years (OR 3,0 [95% IC 1,30-7,09], P = 0,010), twin pregnancies (3.8 [95% IC 1.49-9.99], P = .005), daily maternal smoking above 10 cigarettes (7.1 [95% IC 1.22-41.74], P = .029), maternal obesity (2.2 [95% IC 1.19-4.07], P = .012), endometriosis stages III and IV (6.4 [95% IC 1.52-27.04], P = .011), and history of ovarian hyperstimulation syndrome (OHSS) in early pregnancy (5.7 [95% IC 1.29-24.74], P = .021). Risk increase was independent of pregnancy type (singleton or twin) and allowed the elaboration of 2 nomograms.Conclusions: Our study showed a link between some maternal factors and increase in obstetric complications after IVF. Screening of these factors during preconceptional visit is essential to identify at high-risk pregnancies and adapt their monitoring

IMPACT REPROTOXIQUE D’ADDITIF DIESEL CONTENANT DES NANOPARTICULES DE CERIUM : APPROCHE IN VITRO

International audienc

IMPACT REPROTOXIQUE D’ADDITIF DIESEL CONTENANT DES NANOPARTICULES DE CERIUM : APPROCHE IN VITRO

International audienc

IMPACT REPROTOXIQUE D’ADDITIF DIESEL CONTENANT DES NANOPARTICULES DE CERIUM : APPROCHE IN VITRO

International audienc